Autologous T-cells Transfected With mRNA Encoding HBV-TCR T Cell Therapy in Combination With NUC for Chronic Hepatitis B

Study Evaluating the Safety and Efficacy of Autologous T-cells Transfected With mRNA Encoding Hepatitis-B Virus (HBV)-Antigen-specific T Cell Receptor (TCR) in Combination With Nucleos(t)Ide Analogue (NUC) for Chronic Hepatitis B

This is a single center, single arm, open label study to assess the safety, tolerability and effectiveness of the autologous HBV specific T cell receptor (HBV-TCR) redirected T cells in patients with chronic hepatitis B with ongoing with nucleos(t)ide analogue (NUC) treatment. This study will be conducted sequentially starting with Stage-1, followed by Stage-2.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: TCR-T

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100039
    • The Fifth Medical Center of PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HBsAg Positive, HBeAg Negative, Anti-HBe Positive (with HBeAg seroconversion).
• On first-line treatment with oral nucleoside analogs antiviral drug therapy for more than a year.
• Adequate organ function
• Willing to stop and/or not to be on other immunomodulators during the study period, and to inform in time when other treatments such as glucocorticoids are needed
• Liver biopsy, Fibroscan® or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic HBV infection without evidence of bridging fibrosis or cirrhosis (≥ Metavir 3, recommended cut-off for Fibroscan 9.0kPa)
• Females of childbearing potential must have a negative pregnancy test at Screening (within 3 days prior to first dose) and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy. Willing and able to comply with all study procedures.
• Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.

Exclusion Criteria:

• History of Acute infection, gastrointestinal bleeding, etc. occurring within 28 days prior to study enrollment.
• Advanced liver cirrhosis, Child-Pugh score ≥ 7 or clinical symptoms of liver function decompensation such as ascites and varicose veins
• Positive test for other viral infections, anti-HAV IgM, anti HCV, anti-HDV, anti -HEV and anti-HIV Any item is positive; liver disease caused by other reasons (such as autoimmune liver disease, alcoholic liver disease, non-alcoholic liver disease, drug-induced liver disease and other liver diseases of unknown cause, etc.).
• History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) > 20 ng/mL at Screening. If AFP > 20 ng/mL, hepatic imaging must exclude hepatocellular carcinoma.
• History of having received (in the last 6 months) or currently receiving any other cell therapies
• History of organ transplantation
• History of severe allergic reaction (hives or anaphylaxis) to blood products
• History of any Grade 4 immune-related AE from prior immunotherapy. Any immune-related AE that led to permanent discontinuation that occurred less than 6 months prior to leukapheresis or whole blood collection for production
• Use of any investigational product (IP) within 28 days of study treatment administration.
• Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HBV-TCR T cell infusion; Autologous HBV specific TCR redirected T cells

Biological: TCR-T; Stage-1: Patients will receive three biweekly HBV-TCR T cell infusions at escalating doses, ranging from 1 x 10^5 cells/kg to 5 x 10^6 cells/kg bodyweight (by IV infusion). Patients are to remain on existing HBV NUC treatment. Stage-2: Patients will receive three biweekly HBV-TCR T cell infusions at maximum dose as determined in Stage-1 study. Patients are to remain on existing HBV NUC treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation of HBV-TCR T cell treatment	Incidence of adverse events/serious adverse events	Start of Treatment until 28 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the capability of HBV-TCR T cell treatment to lower the levels of serum HBsAg	This is based on quantitative changes of HBsAg levels from baseline	Start of treatment until 12 months post treatment follow-up

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Investigators: Principal Investigator: Fu-Sheng Wang, MD, Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: LTCR-CHB-2-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No